1. Field of the Invention
This invention relates to a method for propagating and/or maintaining cells in vitro. More specifically this invention relates to a method for propagating cells on a surface of a hollow fiber membrane.
2. Description of the Prior Art
The cultivation of vertebrate animal cells in vitro i.e. apart from the host animal has long been known. It is generally considered that the first such cultivation was performed in the first decade of this century and involved the growth of infectious canine lymphosarcoma in blood.
In spite of long experience this art or science has come into prominence only in recent years. This prominence is mainly due to the demand for many types of vertebrate animal cells for use in medical and veterinary research and diagnosis, in culturing of infectious agents such as viruses, and in the production of hormones and other biological products. Presently this demand is especially high for mammalian cells, particularly normal mammalian cells which must be attached to a surface for growth, as opposed to growth in a suspension culture.
Numerous procedures have been developed for propagating and/or maintaining attached cells in vitro. Perhaps the most successful prior method involves attaching and growing cells on the interior surface of glass and plastic roller tubes and bottles. Another successful method is by attaching and growing cells on the flat side of appropriately shaped stationary bottles. Many types of cells have been grown by these and other prior art methods with such methods being most successful in growing abnormal or altered cells, that is, cells which possess an abnormal or different number of chromosomes from normal cells of the same type and which have the ability to regenerate an indefinite number of times. However these and other prior methods possess several serious drawbacks, especially in the economical production of large quantities of normal or unaltered mammalian cells. Normal cells in contrast to abnormal cells possess the normal number of chromosomes for the species and regenerate only a relatively predictable number of times before senescence or death.
The principal drawback of prior methods in the propagation of normal mammalian cells arises from the fact that with such methods it is difficult to provide aerobic conditions. Stated otherwise unless the oxygen supply is properly provided in adequate quantities to normal cells the cells will not maintain their normal, differentiated functional state. An additional drawback of prior methods in propagating attached cells, whether normal or abnormal, is the difficulty encountered in attaining tissue-like densities on the growing surface because of problems pertaining to nutrient diffusion within the tissues. Further, prior art methods are not readily adapted to large scale operations and thus are not economically suited for producing large quantities of cells.